Single Parathyroid Adenoma Research Articles

Maximizing Opportunities: Primary Hyperparathyroidism in the Older Adult

Primary hyperparathyroidism creates a multisystem and life-limiting disease burden requiring early recognition to mitigate potential complications. A single parathyroid adenoma is responsible for 80% to 85% of primary hyperparathyroidism, causing subjective cognitive impairment, neuropsychiatric symptoms, osteoporosis-associated bone/joint pain, renal damage, functionality, and poor quality of life. The benefits of treatment include clinically significant fracture risk reduction, improvement in left ventricular hypertrophy, and frailty indices. The criteria for parathyroidectomy to resolve primary hyperparathyroidism are less clear for those over age 85. Evidence-based screening tools are available for advanced practice nurses to quantify the associated risk of complications and poor outcomes.

Innovative Approach of Endosonographic Radioactive Labeling of an Ectopic Parathyroid Adenoma by Technetium-99m Human Serum Albumin: A Case Report

Primary hyperparathyroidism caused by parathyroid adenoma requires surgical resection. To confine the extent of surgery to the very minimum and to exclude an atypical adenoma location, preoperative imaging aims at identifying the suspicious gland. For this purpose, Technetium-99m (99mTc)-sestamibi scintigraphy and SPECT have become the international imaging standard, in inconclusive cases also with C-11 methionine and F-18 choline PET/CT. We present a case of surgery for an ectopic retroesophageal adenoma resected under gamma probe guidance after preoperative radioactive targeting. A 73-year-old patient, who was diagnosed with primary hyperparathyroidism, presented to our outpatient clinic. The patient was symptom-free, but during a routine check-up, parathormone levels of 127 pg/ml (normal range 15-65) were detected. Parathyroid MIBI scintigraphy, including SPECT/CT, failed to locate an adenoma. Therefore, a PET/MRI scan with 164 MBq F-18 choline was applied and a single parathyroid adenoma was detected in a very untypical retroesophageal and prevertebral position, respectively. Due to its esophageal proximity and to enable a very confined surgery, endosonography was performed and the adenoma was transesophageally injected with 75 MBq 99mTc-human serum albumin (HSA). The next day gamma probe-guided minimally invasive resection was performed without any intra- or postoperative complications. Minimally invasive resection of parathyroid adenomas should be the standard but may be difficult in deep collar and atypical locations. Marking the adenoma with a radioactive nanocolloid tracer for gamma probe-guided surgery can be considered an innovative approach to maintain minimal invasive therapy for ectopic adenomas.

A case report to assess the safety and efficacy of Burosumab, an investigational antibody to FGF23, in a single pediatric patient with Epidermal Nevus Syndrome and associated hypophosphatemic rickets

Epidermal Nevus Syndrome (ENS), also known as Cutaneous Skeletal Hypophosphatemia Syndrome or Linear Sebaceous Nevus Syndrome, is caused by a mosaic somatic mutation of RAS (Rat Sarcoma genes) which leads to abnormally elevated levels of fibroblast growth factor 23 (FGF23). FGF23 is a major regulator in phosphate homeostasis. There are multiple disorders, along with Epidermal Nevus Syndrome (ENS), that result in unusually high circulating levels of FGF23. This increase ultimately leads to renal phosphate wasting and reduced levels of 1,25-dihydroxy vitamin D. Across these disorders, the clinical symptoms are similar and often include osteomalacia (hypophosphatemic rickets in children), muscle weakness, fatigue, joint deformities, bone pain, and fractures. Burosumab (KRN23), is an IgG1 monoclonal antibody that binds to the FGF23 receptor and inhibits the activity of FGF23. This leads to an increase in serum phosphate levels. Burosumab emerged as a potential therapy in FGF23 overactivity disorders. Burosumab was successful in the treatment of X-linked hypophosphatemia (XLH) and is now FDA-approved for its treatment. Studies have indicated that Burosumab therapy in subjects with XLH consistently increases and sustains serum phosphorus levels and tubular reabsorption of phosphate without a major impact on urine calcium levels or vitamin D metabolism. We studied the effect of Burosumab treatment in a single pediatric patient with Epidermal Nevus Syndrome. Serum phosphorus rose gradually as we titrated the dose of Burosumab upwards. During treatment, a persistent elevation of parathyroid hormone levels was noted along with a persistent elevation of serum calcium. We presumed the patient had tertiary hyperparathyroidism. However, after the removal of three parathyroid glands, the pathology came back with a single enlarged parathyroid adenoma. Subsequently, his calcium and PTH, and phosphorus levels stabilized while taking only Burosumab.ClinicalTrials.gov NCT04320316.

Variation in parathyroid adenoma size in patients with sporadic, primary hyperparathyroidism: small gland size does not preclude single gland disease.

Small, abnormal parathyroid glands are usually associated with multigland hyperplasia in patients with primary hyperparathyroidism (pHPT). The purpose of this study was to determine the association between parathyroid adenoma size and biochemical cure rates in patients undergoing single gland parathyroidectomy. The study included patients with sporadic pHPT who underwent initial parathyroidectomy and met intraoperative PTH criteria for cure after resection of a single adenoma (SGD). Patients were divided into quartiles (Q1 = smallest) based on gland weight and maximum dimension; cure rates were compared across groups. A single parathyroid adenoma was removed in 517 patients, with a median gland weight of 500 mg (range 50-11890). Median maximum gland dimension was 15 mm (range 5-55). With median follow-up of 28 months (range 6-81), the biochemical cure rate was 97.1%. There was no difference in cure rate by gland weight (Q1 94.6%, Q2 96.9%, Q3 98.4%, Q4 98.5%, p = 0.217) or maximum gland dimension (Q1 95.6%, Q2 97.6%, Q3 97.1%, Q4 98.2%, p = 0.641). When Q1 patients (by gland weight) were divided by quartile, there was no difference in cure rates (93.1% [50-140 mg]; 95.2% [150-190 mg]; 97.1% [200-230 mg]; 93.3% [240-280 mg]; p = 0.665). For patients with pHPT who underwent single gland parathyroidectomy, there was no difference in cure rates by gland weight or maximum dimension. These data suggest that the removal of parathyroid adenomas as small as 50 mg with an appropriate decline in ioPTH likely represent single gland disease and additional exploration may not be necessary.

Parathyroid Computed Tomography: Pearls, Pitfalls, and Our Approach.

Parathyroid imaging is predominantly used for preoperative localization of parathyroid lesions in patients with the biochemical diagnosis of primary hyperparathyroidism. Although imaging algorithms vary, in the era of minimally invasive parathyroidectomy for single parathyroid adenomas, multiphase parathyroid computed tomography (CT) (4-dimensional CT) has emerged as a favored modality for presurgical mapping of parathyroid lesions. Implementation and correct interpretation of these studies can be challenging, although confidence and accuracy improve with experience and volume. This article reviews our approach to parathyroid imaging, focusing on pearls and pitfalls in parathyroid CT with ultrasound as a supportive and complementary modality.

PRIMARY HYPERPARATHYROIDISM: OPTIMIZATION OF ANAESTHESIA

Background and Aims. The majority of cases of primary hyperparathyreosis (PHPT) due to solitary adenoma and require the target surgery. Research of new anesthesia/analgesia methods, which afford to have an opioid-sparing effect, is going. Methods. 127 patients with PHPT were divided into 3 groups: the group STI-BCSPB (n=26) was used combined general anesthesia (GA) with sevoflurane (SEV), the tracheal intubation (TI) with the myorelaxant introduction and bilateral cervical superficial plexus blockade (BCSPB); the group STI (n=82) was used SEV anaesthesia with IT and no BCSPB; the group PLM-BCSPB (n=19) was provided propofol (P) GA with protection air-ways by laryngeal mask (LM) and BCSPB. In both groups (STI-BCSPB and PLM-BCSPB) were used co-analgesics, such as dexamethasone (DXM) 8 mg IV, 2% lidocaine (L) 1,0-1,5 mg/kg IV, metamizole (M) or paracetamol (P) 1 g IV, dexketoprofen (DKTP) 50 mg IV as pre-emptive analgesia 30 min before surgery. Ketamine 25 mg IV was used for induction anaesthesia in these groups. In STI group only opioid with P were used for induction of GA. Duration of surgery (DoS), anaesthesia (DoA), opioid consumption, time from the operation ending until the eyes opening (EyOp), desaturation was measured. All data M±m Results. DoS for STI-BCSPB, STI and PLM-BCSPB was respectively 38.7±2.7, 37.8±1.3 and 35.6±1.7 min (NS), DoA was respectively 63.8±3.1, 59.4±1.4 m and 53,8±2.7 min (p= 0.028 STI vs PLM-BCSPB, p= 0.024 STI-BCSPB vs PLM-BCSPB, the difference is significant (DS). EyOp was 15.4±1.1, 15.6±1.2 and 11.6±0.9 min respectively for STI-BCSPB, STI and PLM-BCSPB (p=0.022 STI vs PLM-BCSPB (DS) and p=0.025 STI-BCSPB vs PLM-BCSPB (DS). Desaturation (SpO2 below 92%) due to residual sedation and the effect of muscles relaxants was observed in 39 (47.6%) and 11 (42,3%) patients in STI and STI-BCSPB during the first 30 min postop compared to 2 cases (10.5%) in PLM-BCSPB (both STI groups were DS vs PLM-BCSPB, chi-square test). The dose of intra-op fentanyl was 334.3±17.1, 256.5±16.9 197.3±15.3 mcg in STI, STI-BCSPB and PLM-BCSPB respectively, (DS for PLM-BCSPB vs other groups, DS between STI groups). Conclusions. Combine methods GA with BCSPB have some benefits over mono GA. Co-analgesics afford to achieve an opioidsparing effect. Under ectomy of single parathyroid adenoma, the use of propofol and BSCPB with the laryngeal mask without muscles relaxants seems more preferable compared to sevoflurane anesthesia with BBSCP and tracheal intubation due to the shorter anesthesia duration, time to eye-opening after surgery, lower desaturation frequency.

Preoperative matching studies in the diagnosis of parathyroid adenoma for primary hyperparathyroidism: Can we avoid intraoperative PTH monitoring?

IntroductionWe aim to determine the utility of intraoperative parathyroid hormone (IOPTH) monitoring in patients with matching preoperative ultrasound and mibi SPECT for primary hyperparathyroidism for a single adenoma. MethodsAll patients who underwent minimally invasive parathyroidectomy (MIP) for pseudohypoparathyroidism (PHP) for a single parathyroid adenoma, were included. An Ultrasound and mibi SPECT were performed in all patients. We defined matching studies when both coincided in the localization of the adenoma. IOPTH was performed in all patients and analyzed in three occasions: a baseline measurement at the anesthetic induction, immediately before, and 15 min after gland excision. Success was defined during the third measurement as a drop of IOPTH of at least 50% compared to the previous maximum value after gland excision. Demographics, intraoperative, postoperative variables and the utility of IOPTH monitoring were analyzed. ResultsA total of 218 MIP were performed. The average age was 60.1 years and 85% were female. Preoperative ultrasound and mibi SPECT coincided 100%. When the adenoma was localized, 15 min after its excision, IOPTH did not decrease in 9 patients (4.2%. OR 1.9%–7.69%); all of them underwent a bilateral neck exploration. The added-value of IOPTH accuracy for disease cure was 3.6%. There was a 99% of cure rate. The mean surgical time was 66.4 min and the waiting time for the third IOPTH result was 31 min. Performing IOPTH monitoring made the surgery about twice more expensive. ConclusionsPreoperative matching ultrasound and mibi SPECT for parathyroid adenoma localization in PHP, could avoid IOPTH monitoring in minimally invasive parathyroidectomies.

Association of biochemical and clinical parameters with parathyroid adenoma weight. Turkish-Bulgarian endocrine and breast surgery study group, hyperparathyroidism registry study

Primary hyperparathyroidism (pHPT) caused by a single benign parathyroid adenoma is a common endocrine disorder that is affected by regional differences. Living in different geographical regions reveals differences in the laboratory results and pathological findings, but studies on this subject are not sufficient. The article focuses on biochemical and pathological effects of geographical differences in parathyroid adenoma. In addition, the present study seeks to elaborate on treatment methods and effectiveness of screening in geographical area of Bulgaria and Turkey. In this prospective study, 159 patients were included from 16 centres. Demographic characteristics, symptoms, biochemical markers and pathologic characteristics were analysed and compared between 8 different regions. Patients from Turkish Black Sea had the highest median serum calcium (Ca) level, whereas patients from Eastern Turkey had the lowest median serum phosphorus (P) level. On the other hand, there was no significant difference between Ca, parathormone (PTH) and P levels according to regions. Patients from Eastern Turkey had the highest adenoma weight, while patients from Bulgaria had the lowest adenoma weight. The weight of adenoma showed statistically significant differences between regions (p<0.001). There was a correlation between adenoma weight and serum PTH level (p=0.05) and Ca level (p=0.035). This study has provided a deeper insight into the effect of the regional differences upon clinicopathological changing and biochemical values of pHTP patients with adenoma. Awareness of regional differences will assist in biochemical screening and treatment of this patient group.

Ectopic parathyroid adenoma with acute pancreatitis in a pediatric patient

Abstract Introduction: Hypercalcemia due to primary hyperparathyroidism (PHPT) is uncommon in children with an incidence of 2 to 5 in 100,000 children and adolescents. Primary hyperparathyroidism in children has a bimodal distribution that reflects different etiologies in very young and older children. PHPT is typically caused by a single parathyroid adenoma. Ectopic parathyroid adenomas account for 20% to 22% of primary hyperparathyroidism cases and are rare in children but should be considered in cases that present with hypercalcemia. Patient concerns: We report the case of a 13-year-old girl with PHPT who presented with an unusual presentation of acute pancreatitis and persistent hypercalcemia. Diagnosis: Tc-99m-sestamibi scanning and chest computed tomography scan with contrast showed an anterior mediastinal lesion at the midline embedded into the thymus and was diagnosed as an ectopic anterior mediastinal parathyroid adenoma. Interventions: The genetic test results of whole-exome sequencing were negative. After thoracoscopic and thymus excision, the patient's serum calcium level immediately normalized. Outcomes: Intact parathyroid hormone, serum calcium, and alkaline phosphatase levels returned to normal within two months. Conclusion: PHPT may present with acute pancreatitis, generalized fatigue, and muscle pain as presented in this patient and need a high index of suspicion for early diagnosis. Delayed diagnosis of PHPT can cause end-organ damage; timely diagnosis is especially critical to preserving bone and renal function.

English

Parathyroid glands, minute endocrine glands, located in posterior aspect of thyroid glands secrete parathormone which plays an important role in maintaining calcium homeostasis in the body. The superior and inferior parathyroid glands originate from the 4th and 3rd branchial pouches respectively and migrate to occupy their normal positions in relation to the thyroid gland.1 Hyperparathyroidism is defined as hyper functioning of parathyroid gland and can be primary, secondary or tertiary. Primary hyperparathyroidism is due to parathyroid gland proliferative disorders which include parathyroid adenoma, parathyroid hyperplasia, parathyroid carcinoma or in association with other conditions in MEN syndrome. In more than 90 % patients, primary hyperparathyroidism is caused by a single parathyroid adenoma. Very rarely double parathyroid adenomas are seen. Secondary Hyperparathyroidism is caused in response to any chronic hypocalcaemic conditions like renal failure, gastrointestinal malabsorption, dietary rickets &amp; drugs, like phenytoin, phenobarbital &amp; laxative. Prolonged secondary hyperparathyroidism leads to tertiary hyperparathyroidism due to autonomous secretion. The clinical presentation of hyperparathyroidism is classically described as kidney stones, abdominal groans, painful bones, psychic moans, and fatigue overtones. In the initial course of the disease, the patients present with vague symptoms of fatigue, muscle and joint pain, frequent urination, nausea, constipation, and decreased appetite. If high index of suspicion is maintained, they can be conveniently diagnosed by routine blood tests which show increased calcium levels. However, in India still majority of people are diagnosed when they present with palpable neck mass, skeletal manifestations or deranged renal function. We hereby present 5 cases of parathyroid adenoma managed at our centre over a period of 2 years. P

A Challenging Diagnosis of Primary Hyperparathyroidism in an Adolescent Female

Background: Hypercalcemia secondary to primary hyperparathyroidism (PHPT) is less common in children than adults. Single parathyroid adenoma is commonly the cause of primary hyperparathyroidism in children. Clinical Case: We present a 15-year-old female with one-week history of abdominal pain despite taking over the counter antacids. Her initial work up by her primary care provider revealed serum calcium of 11.8 mg/dL (9.0–11.5) and creatinine of 0.8 mg/dL (0.4–1.2). A week later, she presented to the emergency department with same complaint. In ED, she was found to have hypercalcemia (12.8 mg/dl) with elevated parathyroid hormone (PTH) at 78.5 pg/mL (15–65). Her random urine calcium creatinine ratio was high at 2.1. Her 25OHD was 25 ng/mL (30–100). She had negative urine pregnancy test but had trace ketones, leukocyte esterase, blood and bacteria. CBC and CMP were otherwise unremarkable. She continued to complain abdominal pain with nausea, decrease appetite, fatigue, and general muscle weakness. There was no known family history of calcium or metabolic bone disorders. Her vital signs and physical exam were normal. Subsequent labs showed mild improvement of calcium between (11–12.3 mg/dL), PTH between 54.5 and 77 pg/mL, normal thyroid function. Ionized calcium was mildly elevated 6.0 mg/dL (4.5–5.3) but her repeat 25OHD was low at18 ng/mL. Serum phosphorus levels were relatively normal with lowest level of 2.5 mg/dL (2.7–4.5). Gliadin Deamidated IgA was detectable 15 U/mL (< 15.0 U/). Ultrasound of abdomen was significant for nonspecific mild hepatomegaly; kidneys were normal in size and appearance. Ultrasound of thyroid was significant for probably intrathyroid parathyroid, measuring 6 x 8 x 8 mm. Tc-Sestamibi scan did not confirm a parathyroid adenoma. Genetic testing for MEN-1 was negative. FHH- related genes (i.e. CASR) was positive for p.R990G variant resulting in a mild gain of function of the calcium-sensing receptor. Although previous Tc-Sestamibi scan was unremarkable, an over read of it raised a concern for questionable uptake in the left superior lobe. SPEC-CT demonstrated possible abnormal parathyroid tissue in the upper pole of the left thyroid. FNA of the left thyroid nodule confirmed likely intrathyroidal parathyroid adenoma. Subsequent follow up and treatment, including parathyroidectomy, was done by another institution. She underwent a left parathyroidectomy with normalization of serum calcium and PTH levels post operatively (10.1 mg/dl and 8 pg/mL, respectively) and has complete resolution of her previous abdominal and gastrointestinal symptoms. Conclusion: PHPT is uncommon in children and adolescents and is typically associated with a single parathyroid adenoma. High index of suspicion is key for early diagnosis of PHPT despite a negative Tc-Sestamibi initially.

Rare Case of Severe Hypercalcemia Secondary to Atypical Sestamibi Negative Parathyroid Cystic Adenoma

Primary hyperparathyroidism (PHPT) is defined as excessive secretion of parathyroid hormone (PTH) originating from the parathyroid gland. The most common cause is a single parathyroid adenoma which is typically solid. Cystic parathyroid adenomas (CPA) are the cause of about 1–2% of cases of primary hyperparathyroidism. It is known that cystic parathyroid adenomas are a result of degeneration of an existing parathyroid adenoma. SestaMIBI is an imaging study based on uptake of radioactive technetium99 and used to localize parathyroid adenomas. We describe an unusual case of severe hypercalcemia secondary to 99mTc sestaMIBI negative atypical parathyroid cystic adenoma. A 56-year-old male presented to our facility with nausea and vomiting. His past medical history included hypertension and hepatitis C with no history of fractures or kidney disease. Physical examination was normal. Upon admission the patient was afebrile with blood pressure of 170/120 mmHg and heart rate of 62 bpm. Chemistry showed Calcium of 14.5 mg/dL (8.6–10.2mg/dL), phosphorus 2.2 (2.7–4.5) mh/dL, magnesium 1.8 (1.7–2.6)mg/dL, intact PTH of 375 (15–65) pg/mL, PTH-related peptide <2.0 pmol/L(<2 pmol/L), 25-OH vitamin D of 19 ng/ml (30–80), Creatinine 1.22 (0.7–1.2)mg/dL, alkaline phosphatase 95 (40–129) units/L. He was started on aggressive hydration, calcitonin 4 units/kg, 4 mg of IV Zolendroninc acid. Neck sonogram revealed a large, complex, predominantly anechoic lesion with solid vascular components and thick internal septations in the inferior and medial aspect of the right thyroid lobe measuring 3 x 2 x 5.5 cm. Findings were confirmed with CT of the neck. Since Sestamibi scan (planar and SPECT/CT) did not show uptake in parathyroid glands, the cyst was thought to be of thyroid origin. Fine needle aspiration was not able to detect cellular material, but PTH was >100 pg/ml on the FNA sample. Otolaryngology service was consulted for parathyroidectomy. During the surgical treatment, the right upper parathyroid gland was removed with no changes in serum PTH. Next, the cystic lesion was removed with normalization of serum PTH (from 218 pg/ml to 35.2 pg/ml respectively). Intraoperative frozen section analysis was read as a cystic parathyroid adenoma. The final pathology report revealed cystic parathyroid tissue favoring parathyroid adenoma with focal atypia. Hypercalcemia resolved. Conclusions: Atypical cystic parathyroid adenomas are a rare cause of PHPT. 90% of parathyroid cysts are nonfunctional. Above mention is a case of a patient presenting with hypercalcemic crisis secondary to cystic parathyroid adenoma, which posed a diagnostic challenge as both neck ultrasound and 99mTc sestaMIBI scan were inconclusive. These findings should trigger suspicion for functional parathyroid lesions. Cystic components should be evaluated for PTH levels and if significantly elevated should be treated as a parathyroid adenoma.

An Unusual Presentation of Primary Hyperparathyroidism: Ectopic Parathyroid Gland and Multiglandular Disease

Primary hyperparathyroidism (PHPT) can be associated as a single parathyroid adenoma in approximately 85% of patients, the remaining 15% of them correspond to individuals with hyperplasia. The multiglandular parathyroid disease varies in range 7–33% and contribute a persistent PHPT. We report a case of primary hyperparathyroidism with an unusual presentation of ectopic mediastinal parathyroid. The case was of a 54-year-old female, who started her illness 3 years ago, with frequent headache, regular fatigue and muscle pain, denied losing weight. She was admitted to emergency room for a urinary infection. During the hospitalization showed bilateral nephrocalcinosis, hypercalcemic crisis. She has a background of total thyroidectomy and subtotal parathyroidectomy because a thyroid adenomatous hyperplasia and parathyroid hyperplasia with removal of a total of three parathyroid glands. She had very high PTH level. Laboratory: serum calcium: 16.8mg/dl; ionic calcium: 2.37 mmol/L; P: 1.9 (2.7–4.5g/dL); Hb: 9 g/dL; Platelets: 558 000 per microliter; Leukocytes 9 600 cells/mcL; Albumin: 4g/dl; TSH: 0.06 mU/L; fT4: 1.29 (L-T4 doses were 100 ug). Four months after parathyroid surgery, the intact PTH level dropped from 1602 ng/l to 550 (15–65 ng/L). Computed tomography and Tc-sestamibi scintigraphy - SPECT revealed a residual cervicothoracic mass in retroesophageal region (D1-D2) (Fig1 -2). The patient underwent a new surgery and the intact PTH dropped 39ng/L. Histopathology revealed characteristic features of a parathyroid adenomatous (10 gram weight) (Fig.3); additionally a retroesternal ectopic thyroid tissue. There was not reappearance of high blood calcium and parathormone levels more than 6 months after second surgery for PHPT. An unusual case of PHPT caused by a multiglandular disease parathyroid varies (four glands and a ectopic gland), reliable histopathologic adenomatous and hyperplastic parathyroid disease, and persistent primary hyperparathyroidism with very high serum intact PTH level.Reference: (1) Masi L. Primary Hyperparathyroidism. Brandi ML (ed): Parathyroid Disorders. Focusing on Unmet Needs. Front Horm Res. Basel, Karger, 2019, vol 51, pp 1–12. (2) Pecheva M, Mahendran K, Kadlec J, Lofthouse M1, Van Tornout F. Mediastinal giant parathyroid adenoma-a minimally invasive mediastinal surgical approach for an emergency presentation. Ann Cardiothorac Surg. 2016 Jan;5(1):70–3. (3) Cakmak H 1, Tokat AO, Karasu S, Özkan M. Adenoma paratiroideo mediastínico gigante. Tuberk Toraks. 2011; 59 (3): 263–5. (4)Thier M, Daudi S, Bergenfelz A, Almquist M. Predictors of multiglandular disease in primary hyperparathyroidism. Langenbecks Arch Surg. 2018;403(1):103–109.

Occurrence of Hepatocellular Carcinoma in a 40-Year-Old Male With MEN2A Syndrome

Background: Multiple Endocrine Neoplasia Type 2A (MEN 2A) is a genetic syndrome in which the patient is susceptible to the development of: 1. medullary thyroid carcinoma, 2. pheochromocytoma, and 3. parathyroid adenomas or hyperplasia. Our objective is to report the first occurrence of hepatocellular carcinoma in a young adult male with MEN 2A syndrome without prior liver disease.Clinical Case: A 40-year-old male was screened positive for the C634R point mutation of the RET Proto-Oncogene after his sister with MEN 2A syndrome had tested positive. The patient had no history of alcohol or drug abuse. His family history was remarkable for the deaths of his mother and maternal grandmother from unknown malignancies at the ages of 35 and 45 respectively. His physical exam revealed a BP of 135/85mm Hg, BMI 26 kg/m2 and palpable bilateral thyroid nodules. Lab tests included a calcitonin of 131 pg/ml, (0.0-8.4 pg/ml), calcium 11.4 mg/dL (8.4-10.3 mg/dL), parathyroid hormone (PTH) 1765 pg/ml (12-65 pg/ml), ALK PHOS 1856 U/L (20-120 U/L), ALT 16 U/L (<39 U/L), Albumin 4.1gm/dl (3.4-5.0gm/dl), plasma normetanephrine 0.95 nmol/L (0.00- 0.89 nmol L) and urine metanephrines 291 pg/d (62-207 pg/d). A CT scan demonstrated hyperdense 12 mm right and 5 mm left adrenal nodules, both confirmed MIBG positive. Neck ultrasound showed bilateral thyroid nodules, the largest measuring 1.1 x 0.8 x 1.1 cm in the right lobe and a 3.5 x 2.2 x 2.1 cm heterogeneous mass posterior to the right thyroid lobe. The patient was prepped with doxazosin and underwent a laparoscopic right adrenalectomy then 2 months later a total thyroidectomy with neck lymph node dissection, resection of the right parathyroid tumor mass and bilateral inferior parathyroid glands. Surgical pathology confirmed the right adrenal pheochromocytoma, multifocal bilateral medullary thyroid cancer with 1 of 70 neck lymph nodes positive and a single large parathyroid adenoma. He received levothyroxine to maintain euthyroidism. Within 6 months of his surgery, calcitonin was < 2 pg/ml, CEA 2.3 U/ml (<5.0 U/ml) and ALK PHOS 44 U/L. Urine metanephrines remained mildly elevated 291 pg/d (62-207 pg/d). Serial abdominal CT imaging revealed no change of the left adrenal mass but three new bi-lobar 1-2 cm enhancing liver lesions. CT guided needle biopsies of the liver masses revealed hepatocellular cancer without evidence of cirrhosis. The patient underwent successful thermal ablation of all 3 liver lesions. Laboratory evaluation was negative for Hepatitis A, B and C. His alpha fetal protein level has remained stable in the range of 4.7 to 5.8 ng/ml (<15ng/ml).Conclusions: This is the first reported case of hepatocellular carcinoma in a patient with MEN 2A syndrome who had no predisposing liver disease, raising suspicion that his germline RET mutation contributed to his liver cancer.

Post-Traumatic Heterotopic Ossification With Incidental Hyperparathyroidism

Background: Heterotopic ossification (HO) is a rare disease characterised by abnormal bone growth in non-osseous tissues, causing pain, immobility and impaired quality of life. Although still being elucidated, the underlying pathophysiology may relate to local macrophage-driven inflammation in response to trauma1. Case: A 35-year-old man involved in a motor vehicle accident (MVA) fractured over twenty bones (multiple vertebrae, ribs and complex open book pelvic fracture with shattered left acetabulum) with extensive soft tissue injuries requiring multiple surgeries. Past medical history included a renal calculus three years earlier. His serum corrected calcium on admission was elevated at 2.87mmol/L (2.10-2.60mmol/L). Peri-operative fluid over-resuscitation necessitated boluses of intravenous furosemide, and serum calcium transiently normalised before rapidly incrementing and peaking at 3.04 mmol/L. Serum parathyroid hormone post-operatively was inappropriately high at 9.4pmol/L (1.0–7.0pmol/L) and 25-hydroxyvitamin D low at 24nmol/L (50-150nmol/L). Oral vitamin D replacement was commenced and he received intravenous pamidronate (3x60mg infusions) which briefly restored normocalcaemia. Neck ultrasound and sestamibi scintigraphy demonstrated a left parathyroid adenoma, and he underwent parathyroidectomy. Histology revealed a single parathyroid adenoma. He has been normocalcaemic since surgery. Despite excellent overall recovery, mobility at the left hip remained restricted in all planes of movement. He could not perform simple activities such as putting on his shoe. Plain radiographs showed HO lateral to the left acetabulum, femoral head and neck, with bony bridging to the left ilium on computed tomography. Bone turnover markers (BTMs) measured eleven months post-MVA (and pamidronate) were elevated, with CTX of 750ng/L (100-600ng/L) and P1NP of 207ug/L (15-80ug/L). BTMs gradually reduced over time, plateauing two years post-MVA (CTX 480ng/L and P1NP 103ug/L). Surgery with pre-operative radiotherapy to remove the left hip HO is now planned. Discussion: This man had multiple recognised risk factors for HO, including male sex, trauma followed by immobilisation and pelvic fracture. His hyperparathyroidism may have predisposed HO development through excess calcium-phosphate product promoting soft tissue calcification. Bisphosphonates may also increase the risk2. Elevated BTMs have been demonstrated in the early phase of HO; further research may elucidate whether BTMs can guide timing of surgical intervention relative to the pathophysiological processes driving HO.

Predictors of adenoma size and location in primary hyperparathyroidism

PurposeIn primary hyperparathyroidism (PHPT), intraoperative localization of the parathyroid adenoma can be challenging, especially in cases of negative preoperative imaging. Since a focused unilateral parathyroidectomy has benefits compared to a conventional bilateral neck exploration, the question arises whether adenoma size prediction can facilitate a targeted approach. We investigated whether single parathyroid adenoma size can be estimated using preoperative parathyroid hormone (PTH), calcium, and phosphate in patients with PHPT. Preoperative imaging accuracy was evaluated.MethodsThe data of 156 patients who underwent curative parathyroidectomy for single adenoma PHPT were analyzed retrospectively. Information obtained included laboratory data, imaging results, intraoperative data, and final pathology. Imaging accuracy was analyzed descriptively. The association between preoperative biochemical markers and adenoma dimensions was investigated using Spearman’s correlation coefficient and multivariable regression modeling.ResultsCervical ultrasound correctly predicted adenoma laterality in 95.5%, sestamibi scintigraphy in 80.6%, both had lower true-positive rates for quadrant prediction. Patients with negative imaging results showed higher thyroid volumes than those with positive results. Adenoma volume was positively correlated with preoperative PTH (p < 0.001) and calcium (p < 0.001) and negatively correlated with preoperative phosphate (p = 0.001). Using these preoperative biochemical markers and patient age and BMI, adenoma volume can be significantly predicted using the multivariable regression algorithm.ConclusionCervical ultrasound is superior to scintigraphy for predicting adenoma location and should be the first-choice imaging method, but both methods may be limited by increased thyroid volume. Large adenomas are more likely with higher PTH, higher calcium, and lower phosphate levels. In cases of undetermined adenoma location, an estimation of adenoma volume via our algorithm could corroborate sonographic volume measurements of the suspected adenoma.

Double ipsilateral parathyroid adenomas, with one supernumerary and ectopic at the same time: a case report

BackgroundDouble adenomas (DA) represents a distinct clinical entity of primary hyperparathyroidism (PHPT). DA may follow various embryologic distribution patterns and could be supernumerary and/or ectopic.Case presentationWe describe the first case of PHPT which comes as a result of double ipsilateral adenoma, of which one was both ectopic and supernumerary. A 45 year-old Greek male patient with diagnosed PHPT due to a single lower right parathyroid adenoma was admitted to our department for surgical treatment. The preoperative tests (neck US, Sestamibi scan) were conclusive for single gland disease. The patient underwent focused parathyroidectomy. The frozen section revealed a parathyroid adenoma with a slight possibility for parathyroid carcinoma. Ten minutes after the excision, intact PTH (iPTH) dropped >50% related to preoperative values and was within normal range. Right hemithyroidectomy with additional ipsilateral central neck dissection was performed, because of the possibility for parathyroid carcinoma. The final pathology report showed that the first excised tissue proved to be a parathyroid adenoma, while a second subcapsular one and a normal right upper parathyroid gland were also found.ConclusionsPreoperative localization of DA using routine imaging tests and the utility of intraoperative parathyroid hormone assay are still unreliable in detecting multiple adenomas. Furthermore, a slight possibility of a second and simultaneously supernumerary and ectopic adenoma maybe present. Therefore, it would be advisable to establish the use of more advanced imaging tests (such as 4D-CT, 4D-MRI) or other diagnostic tools when DA are suspected.

POS-090 PRIMARY HYPERPARATYHROIDISM: A NEPHROLOGIST EXPERIENCE

Primary hyperparathyroidism (PHPT) is a common endocrine disorder frequently encountered in everyday practice. It classically presents with hypercalcemia which is the hallmark of the disease in association with inappropriately normal to high levels of PTH . The clinical presentation may vary from asymptomatic to symptomatic disease with eventual complications, for instance skeletal and renal abnormalities. It may be due to a single benign parathyroid adenoma which is by far the most common cause or a multiglandular disease in the familial forms Herein is a retrospective and descriptive single-center study of PHPT observed among patients between 2010 and 2020 realized in our department of nephrology in Monastir Tunisia. 10 patients were gathered. The mean age was 58.5 years ranging from 27 to 87 years . The sex ratio was1 :1. Hypertension was found in 5 patients (50 %) : 3 females and 2 males. 1 patient was found to have diabetes. Lithiasis occured in 3 patients all of whom were women and nephrocalcinosis occured in 2 patients. There were no vascular calcifications nor pain in any patient. The average hemoglobin was 9.2 g/dl ranging from 8 to 11.3 g/dl. All patients had hypercalcemia with a mean of 3.09 mmol/l. 5 patients had hypophosphatemia (50 %). PAL was available in 5 patients all of whom had elevated levels with a mean of 190.8 UI/ml. The mean creatinine level was 196.2 umol/l. Cervical ultrasound was performed in all patients and came back normal in 6 patients (60%). In the remaining patients, it has shown bilateral or unilateral lobules. Scintigraphy was also performed in all patients and findings were consistent with those found in the 4 patients with ultrasound abnormalities but has shown anomaly in 4 of the 6 patients (66%) in whom ultrasound came back normal. One patient had developed a brown tumor. Total parathyroidectomy was performed in 6 patients and partial parathyroidectomy in 2 patients. In the post-operative follow-up, all of the patients have normalized their calcemia levels , 5 patients have normalized their kidney function (50%) and the diagnosis of acute kidney injury secondary to hypercalcemia was retained. PHPT affects women 3 to 4 times more than men but in our study they were similar. Hypercalcemia was the most important biological sign.

Autofluorescence pattern of parathyroid adenomas.

BackgroundPrimary hyperparathyroidism (pHPT) is a common endocrine pathology, and it is due to a single parathyroid adenoma in 80–85 per cent of patients. Near-infrared autofluorescence (NIRAF) has recently been used in endocrine surgery to help in the identification of parathyroid tissue, although there is currently no consensus on whether this technique can differentiate between normal and abnormal parathyroid glands. The aim of this study was to describe the autofluorescence pattern of parathyroid adenoma in pHPT.MethodsBetween January and June 2019, patients with pHPT who underwent surgical treatment for parathyroid adenoma were enrolled. Parathyroid autofluorescence was measured.ResultsTwenty-three patients with histologically confirmed parathyroid adenomas were included. Parathyroid adenomas showed a heterogeneous fluorescence pattern, and a well defined autofluorescent ‘cap’ region was observed in 17 of 23 specimens. This region was on average 28 per cent more fluorescent than the rest of the adenoma, and corresponded to a rim of normal histological parathyroid tissue (sensitivity and specificity 88 and 67 per cent respectively). After resection, all patients were treated successfully, with normal postoperative values of calcium and parathyroid hormone documented.ConclusionParathyroid adenomas show a heterogeneous autofluorescence pattern. Using NIRAF imaging, the majority of specimens showed a well defined autofluorescent portion corresponding to a rim of normal parathyroid tissue. Further studies should be conducted to validate these findings.

Delayed sampling of intraoperative parathormone may be unnecessary during parathyroidectomy in kidney-transplanted and dialysis patients.

Introduction:Some authors advise in favor of delayed sampling of intraoperative parathormone testing (ioPTH) during parathyroidectomy in dialysis and kidney-transplanted patients. The aim of the present study was to evaluate the intensity and the role of delayed sampling in the interpretation of ioPTH during parathyroidectomy in dialysis patients (2HPT) and successful kidney-transplanted patients (3HPT) compared to those in single parathyroid adenoma patients (1HPT).Methods:This was a retrospective study of ioPTH profiles in patients with 1HPT, 2HPT, and 3HPT operated on in a single institution. Samples were taken at baseline ioPTH (sampling at the beginning of the operation), ioPTH-10 min (10 minutes after excision of the parathyroid glands), and ioPTH-15 min (15 minutes after excision of the parathyroid glands). The values were compared to baseline.Results:Median percentage values of ioPTH compared to baseline (100%) were as follows: 1HPT, ioPTH-10 min = 20% and ioPTH-15 min = 16%; 2HPT, ioPTH-10 min = 14% and ioPTH-15 min = 12%; 3HPT, ioPTH-10 min = 18% and ioPTH-15 min = 15%.Discussion:The reduction was equally effective at 10 minutes in all groups. In successful cases, ioPTH decreases satisfactorily 10 minutes after parathyroid glands excision in dialysis and transplanted patients, despite significant differences in kidney function. The postponed sampling of ioPTH appears to be unnecessary.